Dysregulation or loss of control of cell division can result in the development of any of a variety of cell proliferative disorders, many of which are debilitating or deadly. Although much has been learned about mechanisms involved in cell proliferation, and therefore about common biological principles underlying a variety of different disorders, there remains a need for the development of new and/or improved therapies for the treatment of such conditions.
There is a particular need for the development of improved therapies for the treatment of tumors that express the Ras oncogene. Ras-expressing tumors are often more resistant to standard therapies. Furthermore, many of the most deadly cancers involve Ras-expressing tumors. For example, 90-95% of pancreatic tumors are Ras-expressing. Similarly, 40-45% of colorectal tumors, 40% of bladder tumors, 15-20% of non small cell lung carcinomas express Ras. Indeed, 10-25% of myelodysplastic syndromes (MDS), which are not themselves cancer but are bone marrow disorders characterized by abnormal cell maturation that typically progress to cancer (AML), also express Ras. There is a profound need for the development of therapies for these and other Ras-expressing diseases and disorders.